Reactor foam sensor systems and methods of use

ABSTRACT

A foam sensor system includes a container bounding a compartment. A foam sensor assembly is mounted on the container and includes: a base being secured to the container; a foam contact being spaced apart from the base and disposed within the compartment of the container, at least a portion of the foam contact having a first diameter; and a transition member extending between the base and the foam contact with at least a portion of the transition member being openly exposed within the compartment of the container, at least a portion of the transition member having a second diameter that is smaller than the first diameter, the foam contact and transition member being connected together so that an electrical signal can pass therethrough.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.14/598,881, filed Jan. 16, 2015, U.S. Pat. No. 9,606,077, which claimsthe benefit of U.S. Provisional Application No. 61/928,091, filed Jan.16, 2014, which are incorporated herein by specific reference.

BACKGROUND OF THE INVENTION

1. The Field of the Invention

The present invention relates to foam sensor systems used in reactors,such as bioreactors and fermenters, for controlling foam levels withinthe reactor bags so as to prevent unintentional clogging of the gasexhaust filters.

2. The Relevant Technology

It is now common in the biopharmaceutical industry to use bioreactorswhere the portion of the reactor that contacts the culture of cells isdisposable so that no sterilization or cleaning is required betweendifferent batches. One example of a disposable type reactor includes alarge flexible bag that is disposed within a support housing, the bagcontaining the cell culture that is being grown. A sparger is used todeliver needed gases to the culture while an impeller located within thebag is used to continuously mix the culture. The sparger gas exits outof the bag through a gas exhaust filter.

To help prevent or limit shear damage to the cells caused by theimpeller, a surfactant is typically added to the culture. However, thecombination of the surfactant, waste product from the cells, and thesparger gas passing through the culture results in the continualproduction of foam that collects on top of the culture within thereactor bag. If the produced foam is permitted to continue to build upwithin the reactor bag, the foam will eventually be drawn out of the gasexhaust line with the sparger gas and pass into the gas exhaust filter.Because the foam is very sticky, the foam will almost immediately clogthe filter, thereby causing the reactor to shut down because the spargergas can no longer escape the reactor bag. The scenario is known as“foaming-out.” Once the reactor shuts down, the cells will quickly dieand the entire culture will be lost. As a result, the foaming-out of abioreactor can be extremely expensive due to the loss of the culture,the loss of the previous time and effort used in growing the culture,and the required time and expense to start the process over again with anew reactor bag and culture. In addition, foaming-out can significantlydelay production time.

To help prevent foaming-out, an anti-foaming agent can be added to theculture while it is growing within the reactor bag. The effectiveness ofthe anti-foaming agent, however, is only temporary. As such, thebioreactor must be continually monitored through the production cycleand additional anti-foaming agent added as needed. This process,however, is labor intensive and is prone to failure if the reactor isnot closely monitored. To help eliminate the required monitoring,relatively large quantities of anti-foaming agent are often added to theculture at set time intervals, independent of the foam production. Thisprocess, however, tends to use more anti-foaming agent than is actuallyneeded to control the foam. Using anti-foaming agents and particularlyexcessive amounts of anti-foaming agents can be problematic in that theanti-foaming agent can build up on the surfaces that it contacts, whichcan cause production problems, and because the anti-foaming agenteventually needs to be removed from the culture in a downstreamproduction step. The more anti-foaming agent in the culture, the moredifficult and time consuming it is to remove the anti-foaming agent fromthe culture.

Accordingly, what is needed in the art are reactor systems that limitall or at least some of the above problems.

SUMMARY OF THE INVENTION

One embodiment of the present invention is directed to a foam sensorsystem that can include:

-   -   a container bounding a compartment; and    -   a foam sensor assembly mounted on the container and comprising:        -   a base being secured to the container;        -   a foam contact being spaced apart from the base and disposed            within the compartment of the container, at least a portion            of the foam contact having a first diameter; and        -   a transition member extending between the base and the foam            contact with at least a portion of the transition member            being openly exposed within the compartment of the            container, at least a portion of the transition member            having a second diameter that is smaller than the first            diameter, the foam contact and transition member being            connected together so that an electrical signal can pass            therethrough.

The second diameter of the transition member can be equal to or lessthan ⅓ of the size of the first diameter of the foam contact.Furthermore, the first diameter can be larger than 3 mm and the seconddiameter smaller than 1 mm.

In one embodiment, the transition member can be bent over an angle of atleast 180° without plastic deformation. The transition member can becomprised of a nickel-titanium alloy or a copper-aluminum-nickel alloy.

A ground assembly can be mounted on the container and comprise a groundcontact disposed within the compartment of the flexible bag. The groundassembly can be configured so that an electrical potential can beapplied between the foam contact and the ground contact.

The container can comprise a flexible bag comprised of a polymericmaterial.

BRIEF DESCRIPTION OF THE DRAWINGS

Various embodiments of the present invention will now be discussed withreference to the appended drawings. It is appreciated that thesedrawings depict only typical embodiments of the invention and aretherefore not to be considered limiting of its scope.

FIG. 1 is a partial cross sectional side view of a reactor system thatincludes a foam sensor system;

FIG. 2 is an enlarged partial cross sectional view of a foam sensorassembly shown in FIG. 1;

FIG. 3 is an exploded perspective view of the foam sensor assembly shownin FIG. 2;

FIG. 4 is an enlarged cross sectional side view of one ground assemblyshown in FIG. 1;

FIG. 5 is an exploded perspective view of the ground assembly shown inFIG. 4;

FIG. 6 is a cross sectional side view of an alternative embodiment ofthe ground assembly shown in FIG. 4; and

FIG. 7 is an enlarged view of an alternative embodiment of a groundassembly also shown in FIG. 1.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Before describing the present disclosure in detail, it is to beunderstood that this disclosure is not limited to particularlyexemplified apparatus, systems, methods, or process parameters that may,of course, vary. It is also to be understood that the terminology usedherein is only for the purpose of describing particular embodiments ofthe present disclosure, and is not intended to limit the scope of theinvention.

All publications, patents, and patent applications cited herein, whethersupra or infra, are hereby incorporated by reference in their entiretyto the same extent as if each individual publication, patent, or patentapplication was specifically and individually indicated to beincorporated by reference.

The term “comprising” which is synonymous with “including,”“containing,” “having” or “characterized by,” is inclusive or open-endedand does not exclude additional, unrecited elements or method steps.

It will be noted that, as used in this specification and the appendedclaims, the singular forms “a,” “an” and “the” include plural referentsunless the content clearly dictates otherwise. Thus, for example,reference to a “port” includes one, two, or more ports.

As used in the specification and appended claims, directional terms,such as “top,” “bottom,” “left,” “right,” “up,” “down,” “upper,”“lower,” “inner,” “outer,” “internal,” “external,” “interior,”“exterior,” “proximal,” “distal” and the like are used herein solely toindicate relative directions and are not otherwise intended to limit thescope of the invention or claims.

Where possible, like numbering of elements have been used in variousfigures. Furthermore, alternative configurations of a particular elementmay each include separate letters appended to the element number.Accordingly, an appended letter can be used to designate an alternativedesign, structure, function, implementation, and/or embodiment of anelement or feature without an appended letter. For instance, an element“80” may be embodied in an alternative configuration and designated “80a.” Similarly, multiple instances of an element and or sub-elements of aparent element may each include separate letters appended to the elementnumber. In each case, the element label may be used without an appendedletter to generally refer to instances of the element or any one of thealternative elements. Element labels including an appended letter can beused to refer to a specific instance of the element or to distinguish ordraw attention to multiple uses of the element.

Various aspects of the present devices, systems, and methods may beillustrated with reference to one or more exemplary embodiments. As usedherein, the term “embodiment” means “serving as an example, instance, orillustration,” and should not necessarily be construed as preferred oradvantageous over other embodiments disclosed herein.

Various aspects of the present devices and systems may be illustrated bydescribing components that are coupled, attached, and/or joinedtogether. As used herein, the terms “coupled”, “attached”, “connected”and/or “joined” are used to indicate either a direct connection betweentwo components or, where appropriate, an indirect connection to oneanother through intervening or intermediate components. In contrast,when a component is referred to as being “directly coupled”, “directlyattached”, “directly connected” and/or “directly joined” to anothercomponent, there are no intervening elements present.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which the present disclosure pertains. Although a number ofmethods and materials similar or equivalent to those described hereincan be used in the practice of the present disclosure, the preferredmaterials and methods are described herein.

The present invention relates to foam sensors and foam sensor systemsthat are incorporated into a reactor system for growing cells ormicroorganisms or processing other fluids where foam is generated. Ingeneral, the foam sensor systems automatically and continuously detectwhen excessive foam is produced within a reactor so that a proper amountof an anti-foaming agent can be automatically dispensed into the reactorto prevent unwanted foam buildup. By automatically and continuouslymonitoring the foam level, the inventive foam sensor systems are able tomaintain the produced foam within a desired level to ensure that thefoam does not clog the exhaust gas filter communicating with thereactor. The systems also help to optimize the amount of anti-foamingagent used so as to avoid excessive use of anti-foaming agent.

Depicted in FIG. 1 is one embodiment of a reactor system 10incorporating features of the present invention. Reactor system 10 canfunction as a bioreactor for growing cells or a fermenter for growingmicroorganisms. Reactor system 10 can also be used in the production ofother types of fluids, such as chemicals, beverages, food products, orothers, where it is desired to regulate foaming. Reactor system 10comprises a substantially rigid support housing 12 in which a containersystem 30 is disposed. Support housing 12 has an upper end 14, a lowerend 16, and an interior surface 18 that bounds a compartment 20. Formedat lower end 16 is a floor 22. An encircling sidewall 23 extends up fromfloor 22 toward upper end 14. One or more openings 24 can extend throughfloor 22 and sidewall 23 of support housing 12 so as to communicate withcompartment 20. Upper end 14 terminates at a lip 26 that bounds anaccess opening 28 to compartment 20. If desired, a cover, not shown, canbe hingedly or removably mounted on upper end 14 so as to cover all orpart of access opening 28.

Support housing 12 can come in a variety of different sizes, shapes, andconfigurations. An access port can be formed on support housing 12, suchas on sidewall 23 or floor 22, to permit manual access to compartment20. The access port can be selectively closed by a door. Support housing12 is typically made of metal, such as stainless steel, but other rigidor semi-rigid materials can also be used.

As also depicted in FIG. 1, container system 30 is at least partiallydisposed within compartment 20 of support housing 12 and is supportedthereby. Container system 30 comprises a container 32 having a pluralityof tube ports 33 mounted thereon. In the embodiment depicted, container32 comprises a flexible bag having an interior surface 38 that bounds achamber 40 suitable for holding a fluid 41. More specifically, container32 comprises a sidewall 42 that, when container 32 is inflated, has asubstantially circular or polygonal transverse cross section thatextends between a first end 44 and an opposing second end 46. First end44 terminates at a top end wall 48 while second end 46 terminates at abottom end wall 50. Fluid 41 can comprise a biological culture or otherfoam generating fluid as discussed above.

Container 32 is comprised of a flexible, water impermeable material suchas a low-density polyethylene or other polymeric sheets or films havinga thickness in a range between about 0.1 mm to about 5 mm with about 0.2mm to about 2 mm being more common. Other thicknesses can also be used.The material can be comprised of a single ply material or can comprisetwo or more layers which are either sealed together or separated to forma double wall container. Where the layers are sealed together, thematerial can comprise a laminated or extruded material. The laminatedmaterial comprises two or more separately formed layers that aresubsequently secured together by an adhesive.

The extruded material comprises a single integral sheet that comprisestwo or more layers of different material that are each separated by acontact layer. All of the layers are simultaneously co-extruded. Oneexample of an extruded material that can be used in the presentinvention is the Thermo Scientific CX3-9 film available from ThermoFisher Scientific. The Thermo Scientific CX3-9 film is a three-layer, 9mil cast film produced in a cGMP facility. The outer layer is apolyester elastomer coextruded with an ultra-low density polyethyleneproduct contact layer. Another example of an extruded material that canbe used in the present invention is the Thermo Scientific CX5-14 castfilm also available from Thermo Fisher Scientific.

The material is approved for direct contact with living cells and iscapable of maintaining a solution sterile. In such an embodiment, thematerial can also be sterilizable such as by ionizing radiation.Examples of materials that can be used in different situations aredisclosed in U.S. Pat. No. 6,083,587 which issued on Jul. 4, 2000 and USPatent Publication No. US 2003/0077466 A1, published Apr. 24, 2003 whichare each hereby incorporated by specific reference.

In one embodiment, container 32 comprises a two-dimensional pillow stylebag wherein two sheets of material are placed in overlapping relationand the two sheets are bounded together at their peripheries to forminternal chamber 40. Alternatively, a single sheet of material can befolded over and seamed around the periphery to form internal chamber 40.In another embodiment, container 32 can be formed from a continuoustubular extrusion of polymeric material that is cut to length and theends seamed closed.

In still other embodiments, container 32 can comprise athree-dimensional bag that not only has an annular sidewall but also atwo-dimensional top end wall 48 and a two-dimensional bottom end wall50. Three-dimensional container 32 comprises a plurality of discretepanels, typically three or more, and more commonly four or six. Eachpanel is substantially identical and comprises a portion of thesidewall, top end wall, and bottom end wall of container 32.Corresponding perimeter edges of each panel are seamed together. Theseams are typically formed using methods known in the art such as heatenergies, RF energies, sonics, or other sealing energies.

In alternative embodiments, the panels can be formed in a variety ofdifferent patterns. Further disclosure with regard to one method ofmanufacturing three-dimensional bags is disclosed in US PatentPublication No. US 2002/0131654 A1, published Sep. 19, 2002 which ishereby incorporated by specific reference.

Container 32 is typically sterilized so that interior surface 38 andchamber 40 are sterile prior to delivering fluid 41 into chamber 40. Itis appreciated that container 32 can be manufactured to have virtuallyany desired size, shape, and configuration. For example, container 32can be formed having chamber 40 with a volume that is greater than, lessthan, or substantially equal to 10 liters, 30 liters, 100 liters, 250liters, 500 liters, 750 liters, 1,000 liters, 1,500 liters, 3,000liters, 5,000 liters, 10,000 liters or other desired volumes. The sizeof the compartment can also be in the range between any two of the abovevolumes. Although container 32 can be any shape, in one embodimentcontainer 32 is specifically configured to be complementary orsubstantially complementary to compartment 20 of support housing 12. Itis desirable that when container 32 is received within compartment 20,container 32 is generally uniformly supported by support housing 12.Having at least generally uniform support of container 32 by supporthousing 12 helps to preclude failure of container 32 by hydraulic forcesapplied to container 32 when filled with fluid.

Although in the above discussed embodiment container 32 is depicted anddiscussed as a flexible bag, in alternative embodiments it isappreciated that container 32 can comprise any form of collapsiblecontainer or semi-rigid container. Container 32 can also be transparentor opaque and can have ultraviolet light inhibitors incorporatedtherein.

Mounted on sidewall 42, top end wall 48, and bottom end wall 50 are aplurality of tube ports 33 which are in fluid communication with chamber40. Each tube port 33 typically comprises a tubular stem 34 that passesthrough a hole on container 32 and an annular flange 35 that encirclesand radially outwardly projects from stem 34. Flange 35 is welded tointerior surface 38 of container 32 so as to seal closed the openingthrough which stem 34 passes. It is appreciated that any number of tubeports 33 can be present depending on the intended use of container 32and that tube ports 33 can be a variety of different types, sizes andconfigurations. For example, tube ports 33 can be rigid or flexible andstem 34 can be formed having a substantially cylindrical configurationor formed with an outwardly encircling barb. One example of a tube portthat can be used is disclosed in U.S. Pat. No. 7,879,599 which issuedFeb. 1, 2011 and which is incorporated herein in its entirety byspecific reference.

Each tube port 33 can serve a different purpose depending on the type ofprocessing to be undertaken. For example, as will be discussed below ingreater detail, tube port 33A is mounted on top end wall 48 and iscoupled with a fluid line 52 for dispensing media, cultures, nutrients,components and/or other types of fluids and additives into chamber 40 ofcontainer 32. Tube port 33B is also mounted on top end wall 48 and iscoupled with a dispenser 54 that can be activated to dispense apredetermined quantity or flow rate of anti-foaming agent into chamber40 of container 32.

Tube port 33C is mounted on top end wall 48 and is coupled to one ormore exhaust gas filters 58, either directly or through a gas exhaustline 56. Filter 58 enables gas to exit out of container 32 whilepreventing any contaminates from entering container 32. Filter 58 canalso be used to remove any contaminates and/or moisture from the exhaustgas as it passes through filter 58. One example of a filter that can beused is a sterilizing filter that can remove contaminates down to 0.2microns. Other filters can also be used.

More specifically, filter 58 comprises a porous material through whichgas can pass but through which unwanted contaminants, such as bacteriaand microorganisms, cannot. The porous material is typically hydrophobicwhich helps it to repel liquids. For example, filter 58 can be comprisedof polyvinylidene fluoride (PVDF). Other materials can also be used.Where the system is acting as a bioreactor or fermentor, filter body 58,or the porous material thereof, typically needs to operate as asterilizing filter and will thus typically have a pore size of 0.22micrometers (μm) or smaller. The term “pore size” is defined as thelargest pore in the material through which a particle can pass.Commonly, the porous material of filter 58 has a pore size in a rangebetween 0.22 and 0.18 However, for pre-filtering applications or fornon-sterile applications, the porous material for filter 58 can have alarger pore size, such as in a range between about 0.3 and 1.0 μm. Instill other applications, the pore size can be greater than 1.0 μm. Oneexample of filter 58 is the DURAPORE 0.22 μm hydrophobic cartridgefilter produced by Millipore. Another example is the PUREFLO UEcartridge filter available from ZenPure.

If desired, a condenser 60 can be disposed between port 33C and filter58 so that the exhaust gas passes through condenser 60. Condenser 60 canbe used to remove moisture from the exhaust gas before the exhaust gasreaches filter 58. Condenser 60 thus helps to remove moisture that canclog filter 58. The condensed moisture can either be returned tocontainer 32 or separately collected. One example of a condenser thatcan be used as condenser 60 and the remaining components needed tooperate the condenser are disclosed in U.S. Pat. No. 8,455,242 whichissued on Jun. 4, 2013 and which is incorporated herein in its entiretyby specific reference. Another example of filters and condensers thatcan be used is disclosed in U.S. patent application Ser. No. 14/588,063,filed Dec. 31, 2014, which is incorporated herein in its entirety byspecific reference. Other condensers and filters can also be used.

Tube port 33D is mounted on bottom end wall 50 and is coupled to a drainline 62. Drain line 62 can be used for sampling or otherwise dispensingfluid 41 from container 32. Tube ports 33E and 33F are also depicted ascoupled with container 32 on sidewall 42 and their function will bediscussed below. In addition to those depicted, other tube ports canalso be mounted on container 32 for achieving other desired functions.For example, when container 32 is used as a reactor for growing cells ormicroorganisms, other tube ports 33 can be used to attach various probessuch as temperature probes, pH probes, dissolved oxygen probes, and thelike to container 32.

As also depicted in FIG. 1, a sparger 66 is mounted on container 32 fordelivering controlled types and quantities of gases to fluid 41 that isdisposed within container 32. This is the gas that passes out throughgas filter 58. Sparger 66 can come in a variety of different sizes,shapes, and configurations and can be either secured to or freelyresting on or disposed within container 32. One or more spargers can beused and, depending on their function, may emit fine bubbles of gas,larger bubbles of gas, or combinations thereof. The gas that is emittedis typically air, oxygen, nitrogen, or combinations thereof but othergases can also be used. Examples of spargers that can be used aredisclosed in U.S. Pat. No. 7,384,783, issued Jun. 10, 2008, US PatentPublication No. 2006/0270036, published Nov. 30, 2006, and US PatentPublication No. 2013/0082410, published Apr. 4, 2013 which areincorporated herein in their entirety by specific reference. Otherspargers can also be used.

In one embodiment it is noted that sparger 66 can be formed by securinga gas permeable sparger material to flange 35 of a tube port 33G so thatby delivering a gas though stem 34, the gas is forced to travel outthrough the gas permeable sparger material. Further disclosure withregard to the types of materials that can be used for the gas permeablesparger material and how to attach it to flange 35 are also disclosed inthe above referenced US Patent Publication No. 2006/0270036.

Although not always required, in one embodiment means are also providedfor mixing fluid within chamber 40 of container 32. By way of exampleand not by limitation, in one embodiment a drive shaft 68 projects intochamber 40 through a dynamic seal 72 and has an impeller 70 or othermixing element mounted on the end thereof. External rotation of driveshaft 68 thus facilitates rotation of impeller 70 or other mixingelement which mixes and/or suspends fluid 41 within chamber 40. Sparger66 is typically disposed directly below the means for mixing such thatthe mixing or movement of the fluid produced by the mixer helps toentrain the gas bubbles within fluid 41.

In another embodiment of the means for mixing, a flexible tube can bedisposed within chamber 40 having a first end coupled with container 32by a sealed bearing and an opposing second end having an impeller orother mixing element mounted thereon. A drive shaft can be selectivelypassed down the tube and coupled to the impeller so that rotation of thedrive shaft rotates the impeller for mixing fluid 41 but the drive shaftdoes not directly contact fluid 41. In another embodiment, drive shaft65 can be configured to repeatedly raise and lower a mixing elementattached thereto for mixing fluid 41. Alternatively, a magnetic stir barcan be disposed within compartment 40 of container 32 and rotated by amagnetic mixer disposed outside of container 32. In yet otherembodiments, a stir bar, paddle, or the like that projects intocompartment 40 of container 32 can be pivoted, swirled or otherwisemoved to mix fluid 41. In addition, the mixing can be accomplished bycirculating fluid through chamber 40, such as by using a peristalticpump to move fluid 41 into and out of chamber 40 through a tube havingopposing ends sealed to container 32. Gas bubbles can also be passedthrough the fluid to achieve the desired mixing. Finally, supporthousing 12 and container 32 can be pivoted, rotated or otherwise movedso as to mix the fluid within container 32. Other conventional mixingtechniques can also be used.

Specific examples of how to incorporate a mixer into a flexible bag aredisclosed in U.S. Pat. No. 7,384,783, issued Jun. 10, 2008; U.S. Pat.No. 7,682,067, issued Mar. 23, 2010; and US Patent Publication No.2006/0196501, issued Sep. 7, 2006 which are incorporated herein byspecific reference.

As previously mentioned, the present invention includes a foam sensorsystem that is used to both detect and regulate foam buildup withinchamber 40 of container 32. That is, when reactor system 10 isfunctioning as a bioreactor or fermenter, fluid 41 comprises a cultureof living cells or microorganisms. Fluid 41 has a top surface 76disposed within chamber 40 so that a gap or head space 78 is formedbetween top surface 76 and top end wall 48 of container 32. To oxygenatethe cells/microorganisms within fluid 41 and to otherwise regulate thechemistry within fluid 41, gas is sparged into fluid 41 through sparger66 while the fluid within container 32 is being mixed, such as throughimpeller 70. A surfactant is typically added to the culture to limitunwanted shear forces on the cells or microorganisms caused by theimpeller or other mixing element. The sparged gassed bubbles pass upthrough fluid 41 and then enter gap 78 as a humid exhaust gas. Theexhaust gas passes out of gap 78 through tube port 33C and eventuallyexits into the environment through exhaust gas filter 58. As previouslydiscussed, the exhaust gas can also pass through condenser 60 if neededbefore passing through filter 58. Because of the combination of thesurfactant, the waste from the cells/microorganisms, and the spargingbubbles passing through the culture, a foam progressively begins tobuild up on top surface 76 of fluid 41. If the foam is left unchecked,the foam will eventually pass out through tube port 33C with the exhaustgas where it can enter and clog filter 58. Once filter 58 becomesclogged by the foam, the entire reactor system becomes inoperable andthe system shuts down. As such, the culture within container 32 dies.The foam can also produce buildup and blockage within condenser 60 andcan build up on other process components downstream of tube port 33C.

As depicted in FIG. 1, foam sensor system 80 is provided to detect andregulate unwanted foam buildup on top surface 76 of fluid 41. Foamsensor system 80 comprises, in part, a foam sensor assembly 82 and aground assembly 140 that are electrically connected together by acentral processing unit (CPU) 336. As depicted in FIG. 2, foam sensorassembly 82 includes a housing 87 and a foam sensor 84 coupledtherewith. As depicted in FIG. 3, housing 87 includes a tubular stem 88having annular flange 89 encircling radially outwardly projecting froman end thereof. Stem 88 bounds an opening 86 that longitudinally extendstherethrough. In one embodiment, housing 87 can comprise a tube port 33and thus the designs and alternatives discussed therewith are applicableto housing 87. In other embodiments, housing 87 can be specificallydesigned for and manufactured with foam sensor 84. Foam sensor 84comprises a base 90, a foam contact 92, and a transition member 94 thatextends therebetween.

Base 90 comprises an elongated body 96 that is typically cylindrical andextends between a first end 98 and an opposing second end 100. First end98 terminates at a first end face 102 while second end 100 terminates ata second end face 104. An annular barb 106 encircles and radiallyoutwardly projects from body 96 at a location between first end 98 andsecond end 100. In some embodiments, barb 106 is disposed at or towardsfirst end 98. As depicted in FIG. 2, barb 106 is sized so that when base90 is received within opening 86 of stem 88, barb 106 outwardly pushesagainst the interior surface of stem 88 so as to form a liquid tightseal therebetween. As needed, a tie, crimp, or other clamp can encircleand form a constricting force on the exterior surface of stem 34 so asto enhance the seal against barb 106. Base 90 is comprised of a metal orother electrically conductive material. In one embodiment, base 90 iscomprised of stainless steel. However, other metals can also be used.Furthermore, although base 90 is shown as being formed as a singleintegral member, base 90 can also be formed from multiple membersconnected together and from a plurality of stands of wires bundled,woven, or otherwise secured together, such as a cable. As needed, barb106 can be replaced with other structure that forms a liquid tight sealwith stem 88. In other embodiments, housing 87 can be over-molded ontobase 90 or otherwise secured or fastened thereto so that a liquid tightseal is formed therebetween.

As also depicted in FIG. 2, a socket 108 is formed on first end face 102so as to longitudinally project into body 96. An electrical plug 110having electrical wiring 112 is configured to be received within socket108 in a friction fit connection so that a positive electrical contactis made between plug 110 and base 90. In other embodiments, electricalwiring 112 can be permanently secured to body 96 such as throughsoldering or other electrical connections.

Returning to FIG. 3, foam contact 92 is elongated and extends between afirst end 118 that terminates at a first end face 119 and an opposingsecond end 120 that terminates at a second end face 122. In oneembodiment foam contact 92 has a length between end faces 119 and 122 ina range between 0.5 cm and 15 cm and more commonly between 1 cm and 8 cmor 2 cm and 6 cm. Other dimensions can also be used. Although notrequired, in the depicted embodiment, foam contact 92 has asubstantially cylindrical configuration extending along the lengththereof. In alternative embodiments, contact 92 can have alternativetransverse cross sectional configurations such as polygonal, elliptical,irregular, or the like. Contact 92 is also made of a metal or otherelectrically conductive material and is typically made of stainlesssteel. However, other metals can also be used. Furthermore, althoughcontact 92 is shown as being formed as a single integral member, contact92 can also be formed from multiple members connected together and froma plurality of stands of wires bundled, woven, or otherwise securedtogether, such as a cable.

In contrast to base 90 and foam contact 92, which are typically made ofa relatively rigid metal, in one embodiment transition member 94 can bemade from a highly resiliently flexible wire that is comprised of metalor other electrically conductive material. In one embodiment, transitionmember 94 is made from a memory metal. Examples of memory metals includenickel-titanium alloys such as that commonly sold under the name nitinoland copper-aluminum-nickel alloys. Transition member 94 can be made froma material that enables it to be bent over an angle of at least 90° andmore commonly at least 180°, 270° or at least 360° without plasticdeformation. In alternative embodiments, transition member 94 can bemade of a wire that bends with plastic deformation and is made of eitherthe same or different material from base 90 or foam contact 92. In otherembodiments, transition member 94 need not be a wire but can simplycomprise a relatively small diameter shaft. Furthermore, althoughtransition member 94 is shown as being formed as a single integralmember, transition member 94 can also be formed from multiple membersconnected together and from a plurality of stands of wires bundled,woven, or otherwise secured together, such as a cable. In addition,transition member 94 can be formed as a single unity member with base 90and/or foam contact 92. For example, base 90, transition member 94, andfoam contact 92 could be molded, stamped, or cut so that they form onecontinuous member as opposed to two or more separate members that aresecured together.

Transition member 94 is typically made of a different material than base90 or foam contact 92. Base 90 and foam contact 92 are typically madefrom the same material but it is not required. In one embodiment, toattach transition member 94 to base 90 and foam contact 92, a socket 128is formed on second end face 104 of base 90 while a socket 130 is formedon first end face 119 of foam contact 92. First end 124 of transitionmember 94 is received within socket 128 while second end 126 oftransition member 94 is received within socket 130. A crimp force canthen be applied around a portion of base 90 and foam contact 92encircling transition member 94 so that the opposing ends of transitionmember 94 are held by crimp connection within base 90 and foam contact92. The crimping force can produce a recessed crimp groove 131 on base90 and a crimp groove 132 on foam contact 92. Other methods ofattachment can also be used. In one embodiment the exposed portion oftransition member 94 has a length in a range between 2 cm and 15 cm andmore commonly between 3 cm and 10 cm or 4 cm and 8 cm. Other dimensionscan also be used.

Foam sensor assembly 82 is typically assembled as depicted in FIG. 2.That is, base 90 is received within stem 88 so as to form a liquid tightseal therewith. Second end face 104 of base 92 is also typicallydisposed within opening 86 of stem 88 so that at least a portion offirst end 124 of transition member 94 is disposed within opening 86while second end 126 of transition member 94 is disposed withincompartment 40 of container 32. Foam contact 92 is disposed completelywithin compartment 40 of container 32 and is typically located so thatend face 122 is at a distance between 3 cm and about 25 cm from top endwall 48 of container 32 during operation of reactor system 10 and ismore commonly between 5 cm and 15 cm or 6 cm and 12 cm from top end wall48. Other distances can also be used depending on the application. In analternative embodiment, foam sensor assembly 82 can be mounted onsidewall 42 of container 32 at first end 44. Again, however, in thisembodiment end face 122 is also typically located within the aboveranges from top end wall 48 of container 32 during operation of reactorsystem 10. In both embodiments, the pressure of the gas withincompartment 40 supports container 32 in an inflated position andconcurrently supports foam sensor assembly 82.

By making transition member 94 out of a resiliently flexible wire,container system 30 can be folded or rolled up for storage, transport,and/or sterilization even after foam sensor 84 has been attached withoutrisk of damage to foam sensor 84 or to container 32. That is, transitionmember 94 bends when container system 30 is folded or rolled up so thatfoam sensor 84 does not break or puncture container 32. When container32 is unfolded and inflated, transition member 94 resiliently returns toits original desired configuration. Transition member 94 is also shownas having a smaller diameter than foam contact 92. The benefits derivedfrom having this difference in diameter will be discussed later below.

Foam sensor system 80 also includes ground assembly 140 that acts inconjunction with foam sensor assembly 82. Depicted in FIG. 4 is oneembodiment of ground assembly 140 that has multiple uses. In general,ground assembly 140 comprises a tube assembly 142 (which can also bereferred to herein as a housing), a tube port 33E that couples tubeassembly 142 to container 32, a ground contact 146 coupled to an end oftube assembly 142, and a probe 148 that is received within tube assembly142 and engages with ground contact 146. A more detailed description ofthe elements of ground assembly 140 will now be provided.

As depicted in FIGS. 4 and 5, tube assembly 142 comprises an elongatedflexible probe tube 202 and an elongated flexible sampling tube 204 eachcoupled to a body 206. Body 206 of tube assembly 142 has a generallycylindrical shape with an exterior surface 210 extending between a firstend face 212 and an opposing second end face 214. Body 206 bounds afirst passage 216 and a second passage 218 each extending between firstend face 212 and second end face 214. In one embodiment, first passage216 and second passage 218 extend in adjacent parallel alignment witheach other substantially the full length of body 206. In alternativeembodiments, exterior surface 210 of body 206 can have a variety ofalternative transverse cross sections such as elliptical or polygonal,or irregular.

Probe tube 202 of tube assembly 142 has an interior surface 220 and anopposing exterior surface 222 each extending between a first end 224 anda longitudinally spaced apart second end 226. Interior surface 220bounds a first passageway 228 that longitudinally extends through probetube 202. As discussed below in greater detail, ground contact 146couples with first end 224 of probe tube 202. Second end 226 of probetube 202 is coupled with first end face 212 of body 206 so as tocommunicate with first passage 216 of body 206. In this manner, firstpassageway 228 of probe tube 202 and first passage 216 of body 206combine to form a probe passage 232 having a first end 224 and a secondend 236 at or toward second end face 214 of body 206.

Similar to probe tube 202, sampling tube 204 of tube assembly 142 has aninterior surface 244 and an opposing exterior surface 246 each extendingbetween a first end 248 and a longitudinally spaced apart second end250. Interior surface 244 bounds a second passageway 252 thatlongitudinally extends through sampling tube 204. Second passageway 252is open at first end 248 and second end 250, thus allowing fluidcommunication completely through sampling tube 204. Second end 250 ofsampling tube 204 is coupled with first end face 212 of body 206 so asto communicate with second passage 218 of body 206. In this manner,second passageway 252 of sampling tube 204 and second passage 218 ofbody 206 combine to form a sampling passage 254 having a first end 248and a second end 258 at or toward second end face 214 of body 206,allowing fluid communication therethrough.

At least a portion of sampling tube 204 extends along probe tube 202 inadjacent parallel alignment with first end 248 of sampling tube 204being disposed at or toward first end 224 of probe tube 202. In theembodiment depicted, sampling tube 204 is in adjacent parallel alignmentwith probe tube 202 along the entire length of sampling tube 204. Tofacilitate the parallel alignment, sampling tube 204 is coupled withprobe tube 202 along the entire length of sampling tube 204 such as bybeing integrally molded together or secured together such as by anadhesive or other fasteners. In alternative embodiments, sampling tube204 can be coupled to probe tube 202 at spaced apart locations. As aresult of this coupling, when probe 148 is inserted into probe tube 202,as described below, sampling tube 204 also becomes substantially rigidas it extends into chamber 40 of container 32.

In the embodiment depicted, sampling tube 204 is of a smaller diameterthan probe tube 202. It is appreciated that in alternative embodiments,sampling tube 204 can have a larger diameter than or have the samediameter as probe tube 202. Sampling tube 204 and probe tube 202 eachhave a length in a range typically between about 2 cm to about 40 cmwith about 5 cm to about 25 cm being more common. Other lengths can alsobe used.

Probe tube 202, sampling tube 204, and body 206 can be molded as aunitary integral piece. Alternatively, probe tube 202 and sampling tube204 can be connected to each other and/or to body 206 by welding usingconventional welding techniques such as heat welding, RF energy,ultrasonic, and the like or by using adhesives other any otherconventional attaching or fastening techniques.

In some embodiments, an elongated collection tube 266 bounding a thirdpassageway 268 extends outward from second end face 214 of body 206.Collection tube 266 has a first end 272 coupled with second end face 214of body 206 so as to communicate with sampling passage 254 and has anopposing second end 274. A tubular coupler 280 has a first end 282 withan annular barb formed thereon that can be received within second end274 of third passageway 268 to form a liquid tight connection therewith.Tubular coupler 280 has a second end 284 with an annular barb formedthereon that can be received within a separate fluid line for deliveringfluid collected from sampling tube 204 to a desired location, such as acollection bag or other container. Alternatively, collection tube 266can be used to retrieve fluid or other material from a container toinsert the fluid into chamber 40.

In one embodiment, tube assembly 142 is molded from a soft, resilientlyflexible polymeric material or elastomeric material such aspolyethylene, silicone or KRATON® having a durometer on a Shore A scalewith a value of less than 90 and more preferably less than 70 buttypically greater than 5. In other embodiments, other thermoset orthermoplastic polymers having a durometer in the above range can also beused. Other materials such as those previously discussed with regard tocontainer 32 can also be used. In some embodiments, as a result of thematerial properties, probe tube 202 and sampling tube 204 can bemanually folded over so as to kink the passages therein closed or probetube 202 and sampling tube 204 can be manually pinched, such as by aclamp, to close the passages therein without permanent deformation toprobe tube 202 or sampling tube 204.

Continuing with FIGS. 4 and 5, tube port 33E includes stem 34 andannular flange 35 as previously discussed. In this embodiment, anannular lip seal 288 radially inwardly projects from the interiorsurface of stem 34 at or toward the end from which flange 35 projects.Tube port 33E and the other tube ports disclosed herein can be made ofthe same materials as discussed above with regard to tube assembly 142.Further disclosure and alternative embodiments for tube port 33F are setforth in U.S. Pat. No. 7,879,599, issued Feb. 1, 2011 which isincorporated herein in its entirety by specific reference. Body 206 oftube assembly 142 has a substantially cylindrical configuration that isconfigured to snugly fit within stem 34 of tube port 33F so that aliquid tight seal is formed therebetween.

During assembly, flange 35 is welded to the interior surface ofcontainer 32 so that stem 34 outwardly projects through an openingthereon. Probe tube 202 and sampling tube 204 of tube assembly 142 areadvanced through stem 34 of tube port 33E. Tube port 33 is advanced overbody 206 until end 290 of stem 34 butts against an annular shoulder 292outwardly projecting from the second end of body 206. As depicted inFIG. 4, in this position lip seal 288 radially biases against theexterior surface of body 206 at the first end thereof so as to form asealed engagement therebetween. To provide a more secure engagement andseal between stem 34 and body 206, one or more pull ties, clamps, orother tightening devices can be used. For example, in the embodimentdepicted a plastic pull tie 294 is secured around a portion of tubularstem 34 disposed over body 206 so as to further secure the sealedengagement therebetween. In an alternative method of assembly, flange 34can be welded to container 32 after tube assembly 142 is secured to tubeport 33E.

As also depicted in FIGS. 4 and 5, ground contact 146 comprises acylindrical body 300 having a stem 302 projecting from an end thereofand an annular barb 304 encircling and radially outwardly projectingfrom stem 302. Stem 302 terminates at an end face 306 into which a blindsocket 308 is formed. Ground contact 146 is formed from a metal such asstainless steel or other electrically conductive materials. Duringassembly, stem 302 is received within first end 224 of probe tube 202 sothat annular barb 304 forms a liquid tight seal between ground contact146 and probe tube 202. In the assembled configuration, blind socket 308is aligned and in communication with probe passage 232 of probe tube202.

A fitting 312 is secured to tube assembly 142 so as to be incommunication with the second end of the probe passage 232. Fitting 312comprises a tubular stem 314 that has an interior surface bounding apassageway 316 extending therethrough. Stem 314 has a first end with anannular barb 316 encircling and radially outwardly projecting therefromand an opposing second end with a lure lock thread 318 or otherconnector formed thereon. During assembly, the first end of stem 314 isreceived within the second end of probe passage 232 so that barb 316forms a secured engagement with tube assembly 142.

As previously mentioned, ground assembly 140 also includes probe 148.Probe 148 comprises an elongated probe stem 322 having a first end 324and an opposing second end 326. The connector 328 encircles and ismounted on second end 326 of probe stem 322. In this embodiment,connector 328 comprises a female lure lock. However, other types ofconnectors that mate with fitting 312 can also be used. Electricalwiring 330 is attached to and communicates with probe stem 322 at secondend 326. Probe stem 322 is comprised of a metal or other electricallyconductive material so that an electrical charge or signal can passalong the length of probe stem 322 and into electrical wiring 320. Inone embodiment, probe 148 is also configured to function as atemperature sensor probe, such as a resistance temperature detector(RTD).

During assembly, first end 324 of probe stem 322 is advanced throughfitting 312 along probe passage 232 and into blind socket 308 of groundcontact 146. Probe stem 322 has a close tolerance fit within blindsocket 308 so that an electrical signal or current can be passed betweenground contact 146 and probe 148. To help facilitate a positiveengagement between probe 148 and ground contact 146, probe stem 148 hasa length slightly longer than the combined length of probe passage 232and blind socket 308. As a result, to enable connector 328 to engagewith fitting 312, probe 148, in one embodiment, must be pushed intoprobe passage 232 so that tube assembly 142 stretches a distance beforeconnector 328 reaches and can be secured to fitting 312. This assemblyresults in a positive biasing force between first end 324 of probe 148and ground connector 146 so as to help ensure a good electrical contacttherebetween. Other electrical connections can also be used. Anadditional benefit of securing probe 148 within probe passage 232 asdiscussed above is that it forces sampling tube 204 to project intocontainer 32 so that sampling fluid can be taken at a location away fromthe wall of container 32.

Because probe tube 202 is sealed closed at first end 224 by groundcontact 146, probe 148 or other support inserted into probe tube 202does not directly contact the liquid or other material within chamber 40of container 32. As a result, probe 148 can be inserted and extractedfrom probe passage 232 without fear of any liquid or other materialleaking out of chamber 40 or becoming contaminated by probe 148.Furthermore, because probe 148 does not contact the contents of chamber40, probe 148 can be repeatedly used without the need for sterilizationor cleaning between uses.

In the fully assembled configuration as depicted in FIG. 1, both probe148 of ground sensor 140 and foam sensor 84 are in electricalcommunication with central processing unit (CPU) 336. CPU 336 applies anelectrical potential or voltage between probe 148 (and thus also groundcontact 146) and foam sensor 84. As previously discussed, during theoperation of reactor system 10, foam slowly starts to build on topsurface 76 of fluid 41. Once foam builds up sufficiently high on topsurface 76 so as to contact foam contact 92 of foam sensor 84, anelectrical signal is passed between foam sensor 84 and ground contact146/probe 148 by passing through the foam and through fluid 41.

The electrical signal is sensed by CPU 336 which in turn signalsdispenser 54 to dispense a predetermined quantity of anti-foaming agentinto container 32 which temporarily dissipates or at least diminishesthe foam buildup. CPU 336 can be programed in a variety of differentways to dispense the anti-foaming agent. For example, the anti-foamingagent can be dispensed as a large bolus after which CPU 336 waits for aperiod before checking again for an electrical signal. Alternatively,the anti-foaming agent can be slowly and continuously released once thesignal is detected and then stopped once CPU 336 can no longer detectthe electrical signal. Other methods can also be used. By automaticallyand continually monitoring the foam level using foam sensor system 80,the foam level can be maintained sufficiently low that there is no riskof the foam passing out of gas exhaust port 33C and clogging gas filter58. In addition, foam sensor system 80 only dispenses the amount ofanti-foaming agent needed to maintain the foam within the desired level.As such, less anti-foaming agent is added to the culture and thus lessanti-foaming agent needs to be removed from the culture.

One of the challenges of foam sensor system 80 is that the foam isrelatively sticky and adheres to both the interior surface of container32 and to foam sensor 84. As a result of the gas flowing through gap 78and the humid vapor within gap 78 that can carry small particles offoam, a thin layer of foam can build up on interior surface 38 ofcontainer 32 within gap 78 and on the exposed portion of foam sensor 84within gap 78. In addition, the foam does not generally build up as aneven layer on top surface 76 of fluid 41 but typically builds up inclumps. The clumps may obtain a height that extends up to transitionmember 94 (FIG. 2) before the foam first encounters foam sensor 84.These clumps can also help build up a layer of foam on the interiorsurface of container 32 within gap 78 and on the exposed portion of foamsensor 84 within gap 78. If a continuous layer of foam is formed oninterior surface 38 of container 32 from the top surface 76 of fluid 41to foam sensor 84, an electrical signal (“false signal”) can passbetween foam sensor 84 and ground contact 146 by passing through thefoam layer on container 32 and fluid 41. This false signal will give afalse reading to CPU 336 that the foam layer on fluid 41 has reachedfoam contact 92 and thus trigger the dispensing of anti-foaming agentinto fluid 41 when no anti-foaming agent may be needed. Furthermore,because of the foam layer on container 32, the false reading maycontinue even after the anti-foaming agent is added, thereby resultingin continued or repeated unwanted dispensing of anti-foaming agent intofluid 41.

Foam sensor 84 is specifically designed with transition member 94 havinga smaller diameter than foam contact 92 to help differentiate between atrue signal where the signal is produced as a result of foam building upon top surface 76 of fluid 41 so as to contact foam contact 92 and afalse signal where the signal is produced as a result of a thin film offoam coating the interior surface of container 32 so as to extendbetween foam sensor 84 and fluid 41. Specifically, electricalconductance is in part related to the surface area of an electricalcontact and the volume of the material through which the electricalcurrent passes. Accordingly, the electrical current of the true signalwill always be greater than the electrical current of the false signal.This is true because the volume of foam through which the trueelectrical signal passes between foam sensor 84 and fluid 41 is largerthan the volume of foam through which the false electrical signal passeson interior surface 38 of container 32 between foam sensor 84 and fluid41. Furthermore, because foam contact 92 has a larger diameter thantransition member 94, foam contact 92 will have more surface areacontacting the foam on top of fluid 41 than transition member 94 willhave contacting the thin film of foam on the surface of container 32.

Accordingly, CPU 336 can be programmed so that when the electricalsignal from foam sensor system 80 is below a predetermined value it isassumed to be a false signal and no anti-foaming agent is released butwhen the signal exceeds the predetermined value, it is assumed to be atrue signal and the anti-foaming agent is released as discussed above.The predetermined value on which to determine a true or false signal canbe the measured electrical signal strength or conductivity. For example,in one embodiment, only signals having a conductivity of greater than20μ Siemens and more commonly greater than 30μ Siemens or 40μ Siemenswill be determined to be a true signal. It is appreciated that thepredetermined conductivity value can be set over a wide range dependingon factors such as the amount of voltage applied between foam contact 92and foam ground 146, the relative diameters between transition member 94and foam contact 92, the materials used for the contacts and otherfactors. In other embodiments, the predetermined value can be set at anyvalue between 20μ Siemens and 50μ Siemens. Other values can also beused. Likewise, other measurements, such as current, can also be used asthe predetermined value.

To help differentiate between the true signal and the false signal, foamcontact 92 will typically have a diameter normal to the longitudinallength thereof that is at least 3, 4, 5, 6, 8, or 10 times larger than adiameter of transition member 94 disposed within chamber 40 of container32 as measured normal to the longitudinal length thereof. Expressed inother terms, a diameter of transition member 94 can be at most ⅓, ¼, ⅕,⅙, ⅛, or 1/10 of a diameter of foam contact 92. Because diameters canchange along the length of foam contact 92 and transition member 94, theabove measured and compared diameters for foam contact 92 and transitionmember 94 can be selected as a maximum diameter, minimum diameter,average diameter over the length thereof or a diameter at any locationon or over at least a portion of foam contact 92 and transition member94. Other ratios can also be used. The diameter of foam contact 92 istypically greater than 2 mm, 3 mm, 5 mm, 7 mm or 10 mm or in a rangebetween 2 mm an 10 mm while the diameter of transition member 94 istypically less than 2.5 mm, 2 mm, 1.5 mm, 1 mm, 0.75 mm or 0.5 mm or ina range between 2.5 mm and 0.5 mm. Again, these diameters can be amaximum diameter, minimum diameter, average diameter over the length ora diameter at any location on or over at least a portion of foam contact92 or transition member 94. Other dimensions can also be used. It isnoted that the term “diameter” as used herein refers to a straight lineor the length of such line passing from side to side of thecorresponding structure, through its center, and is not intended tolimit the structure to a circular or any other defined shape. As thediameter of transition member 94 continues to increase above 2 mm, theability to differentiate between the true and false signal decreases.Likewise, as the diameter of transition member 94 decreases,particularly below 0.5 mm, the risk of structural failure of transitionmember increases.

As depicted in FIG. 2, in the assembled state a cavity 91 (comprising aportion of opening 86) is formed in stem 88 extending from flange 89 tosecond end face 104 of base 90. Transition member 94 centrally extendsthrough cavity 91 with an annular gap formed between transition member94 and the encircling interior surface of stem 88. Because the system ispressurized as a result of the inflow of sparging gas, foam willtypically not enter or build up within cavity 91. However, foam canbridge between transition member 94 and tubular stem 88 or flange 89 atthe opening to cavity 91. The bridging typically occurs as a result of aclump of foam contacting and adhering to transition member 94, as aresult of foam colleting within compartment 40 of container 32, andremaining on transition member 94 even when the remainder of the foam isdissipated as a result of the addition of an anti-foaming agent. Thefalse signal can be produced as a result of the foam bridge contactingthe foam build-up on interior surface 38 of container 32, therebycompleting the circuit to ground contact 146, as discussed above.

To help eliminate or minimize the formation of a foam bridge betweentransition member 94 and tubular stem 88/flange 89 (and thereby minimizeany false signal), the diameter of opening 86/cavity 91 within housing87 can be increased relative to the diameter of transition member 94.For example, while the diameter of transition member 94 is typically inthe values as discussed above, the inside diameter of opening 86/cavity91 encircling transition member 94 is typically greater than 5 mm, 10mm, 15 mm, 20 mm, 30 mm, 40 mm or 50 mm. Other dimensions can also used.In general, the larger the diameter, the lower the probability that afoam bridge can be formed and maintained between transition member 94and tubular stem 88/flange 89. Other dimensions can also used. It isalso noted that cavity 91 typically has a depth extending between flange89 to second end face 104 of base 90 that is in a range between 5 mm and50 mm with between 10 mm to 30 mm or 10 mm to 20 mm being more common.Other dimensions can also be used.

As previously mentioned, in some embodiments foam sensor 82 can bedisposed on sidewall 42 (FIG. 1) of container 32 so as to be positionedwithin head space 78. In this embodiment, it is typically preferred thathousing 87 be angled downward relative to the horizontal so thatcondensate that forms within cavity 91 freely flows out of cavity 91 andinto chamber 40 of container 32. This configuration helps to prevent thecondensate from collecting in cavity 91 which could assist in theformation of a false signal, as discussed above. In one embodiment,housing 87 can be positioned so that a longitudinal axis centrallyextending through opening 86 or cavity 91 of housing 87 is disposed at adownward angle relative to the horizontal in a range between about 10°to about 70° with between about 30° to about 45° being more common.Other angles can also be used.

In other embodiments, it is also envisioned that foam sensor 84 could beformed where transition member 94 is eliminated. For example, foamcontact 92 could extend all the way to body 96 and have a constantdiameter along the length thereof by applying a coating or insulativematerial over the center of the foam contact which will not permit thefoam to stick thereto. As such, no false signals would be produced.

It is appreciated that ground assembly 140 can have a variety ofdifferent configurations. For example, depicted in FIG. 6 is oneembodiment of a ground assembly 140A wherein like elements betweenground assembly 140 and 140A are identified by like referencecharacters. The only difference between ground assembly 140A and 140 isthat in ground assembly 140A, tube port 33E has been eliminated. In thisembodiment, an annular flange 340 encircles and radially outwardlyprojects from body 206 and is integrally molded or otherwise formedtherewith. Flange 340 is welded directly to the interior surface ofcontainer 32. In other embodiments, it is appreciated that sampling tube204 can be eliminated from the ground assembly and that probe 148 neednot be designed to function as a temperature sensor. That is, probe 148can be limited to functioning only to conduct the signal that passes toor from foam sensor 84. Examples of other embodiments of tube assemblies142 that can be modified to operate with ground contact 146 aredisclosed in U.S. Pat. No. 7,879,599 which was previously incorporatedherein by specific reference.

Depicted in FIG. 7 is an alternative embodiment of a ground assembly140B that can be used in place of ground assembly 140 or 140A. Groundassembly 140B comprises port 33F as previously discussed (and which canalso be referred to herein as a housing) and a ground contact 146A.Ground contact 146A comprises an elongated body 346 that extends betweena first end 348 and an opposing second end 350. First end 348 terminatesat a rounded nose 352 while second end terminates at an end face 354. Ablind socket 356 is formed on end face 354 and is configured to receivean electrical plug 110A. An annular barb 358 encircles and radiallyoutwardly projects from body 346 at or towards second end 350. Groundcontact 146A is manually inserted within stem 34 of port 33F so thatbarb 358 forms a fluid tight seal with stem 34 while nose 352 projectsinto container 32. Again, an electrical potential or voltage is appliedbetween ground assembly 140B and foam sensor assembly 82 so that anelectrical signal is passed therebetween when foam reaches foam contact92. In other embodiments, port 33F can couple with ground contact 146Ain the same way that housing 87 couples with base 90 as discussed abovewith regard to foam sensor 84. Other designs for a ground assembly canalso be used.

In view of the forgoing, embodiments of the inventive foam sensor systemprovide a number of advantages. Notably, select embodiments provide anautomated mechanism for determining when an anti-foaming agent should bedispersed into container 32 so as to control the foam level withincontainer 32 and thereby avoid the risk that the gas filter will becomeclogged. By using the automated system, less monitoring of the reactoris required. Furthermore, the amount of anti-foaming agent that is usedis minimized, thereby limiting the problems associated with anti-foamingagents and requiring less anti-foaming agent to be removed from theculture. Select embodiments are also designed to enable easy collapsingand folding of container 32 for shipping, transport, sterilization orthe like with minimal risk of damage to the foam sensor assembly orcontainer 32. Select embodiments also provide a mechanism to helpeliminate any false readings that could be produced as a result of foamcoating the interior surface of container 32 and contacting a portion ofthe foam sensor assembly. Other advantages are also achieved.

The present invention may be embodied in other specific forms withoutdeparting from its spirit or essential characteristics. The describedembodiments are to be considered in all respects only as illustrativeand not restrictive. The scope of the invention is, therefore, indicatedby the appended claims rather than by the foregoing description. Allchanges which come within the meaning and range of equivalency of theclaims are to be embraced within their scope.

What is claimed is:
 1. A foam sensor system comprising: a containerbounding a compartment; and a foam sensor assembly mounted on thecontainer and comprising: a base being secured to the container; a foamcontact being spaced apart from the base and disposed within thecompartment of the container, at least a portion of the foam contacthaving a first diameter; and a transition member extending between thebase and the foam contact with at least a portion of the transitionmember being openly exposed within the compartment of the container, atleast a portion of the transition member having a second diameter thatis smaller than the first diameter, the foam contact and transitionmember being connected together so that an electrical signal can passtherethrough.
 2. The foam sensor system as recited in claim 1, whereinthe second diameter is equal to or less than ⅓ of the size of the firstdiameter.
 3. The foam sensor system as recited in claim 1, wherein thefirst diameter is larger than 3 mm and the second diameter is smallerthan 1 mm.
 4. The foam sensor system as recited in claim 1, wherein thetransition member can be bent over an angle of at least 180° withoutplastic deformation.
 5. The foam sensor system as recited in claim 1,wherein the transition member is comprised of a nickel-titanium alloy ora copper-aluminum-nickel alloy.
 6. The foam sensor system as recited inclaim 1, wherein the transition member has an exposed length in a rangebetween 2 cm and 15 cm.
 7. The foam sensor system as recited in claim 1,further comprising a ground assembly mounted on the container andcomprising a ground contact disposed within the compartment of thecontainer, the ground assembly being configured so that an electricalpotential can be applied between the foam contact and the groundcontact.
 8. The foam sensor system as recited in claim 1, wherein thecontainer comprises a flexible bag comprised of a polymeric material. 9.The foam sensor system as recited in claim 1, wherein the foam contactand the transition member are comprised of different materials.
 10. Thefoam sensor system as recited in claim 1, wherein the base comprises: anelongated body having a first end and an opposing second end; and anannular barb encircling and radially outwardly projecting from the body.11. The foam sensor system as recited in claim 1, further comprising anelectrical wire coupled to the base.
 12. The foam sensor system asrecited in claim 1, further comprising: a housing secured to thecontainer and comprising a stem with a flange radially outwardlyprojecting therefrom, the stem bounding an opening; and the base beingat least partially disposed within the opening of the stem.
 13. The foamsensor system as recited in claim 12, further comprising at least aportion of the transition member being disposed within a portion of theopening of the housing.
 14. The foam sensor system as recited in claim1, further comprising: a fluid disposed within the compartment of thecontainer and having a top surface; a gas filled gap being formedbetween the top surface of the fluid and an upper end of the container;a ground contact being in contact with the fluid within the compartment;the foam contact being disposed within the gap within the container soas to be spaced apart from the fluid; and an electrical potential beingapplied between the foam contact and the ground contact.
 15. The foamsensor system as recited in claim 14, further comprising: means formixing the fluid within the compartment of the container; the fluidcomprising a live culture of cells or microorganisms; and a CPUelectrically coupled with the foam contact and the ground contact, theCPU being programed to dispense a quantity of an anti-foaming agent intothe compartment of the container when an electrical signal passesbetween the foam contact and the ground contact within the compartmentof the container.
 16. A method for controlling foam, the methodcomprising: sparging a gas into a fluid located within the compartmentof the container of the foam sensor system recited in claim 1, thesparging gas producing a foam on a top surface of the fluid within ahead space at an upper end of the container; applying an electricalpotential between the foam contact located within the head space at alocation away from the fluid and a ground contact that is at leastpartially disposed within the fluid; and automatically dispensing ananti-foaming agent into the compartment of the container when the foamproduced on the top surface of the fluid touches the foam contact sothat an electrical signal is passed between the foam contact and theground contact.
 17. The method as recited in claim 16, wherein the fluidcomprises a live culture of cells or microorganisms.
 18. The method asrecited in claim 16, further comprising sensing the electrical signaland only automatically dispensing the anti-foaming agent when theelectrical signal exceeds a predetermined value.